Abstract
Leukocyte adhesion deficiency type 1 (LAD-1) is an autosomal recessive primary immunodeficiency, hallmarked by defective polymorphonuclear transmigration. It is caused by mutations in the gene encoding CD18, which interfere with the CD18/CD11 heterodimerization and expression on leukocyte cell surface. LAD-1 diagnosis rests primarily on the measurement of CD18 expression. However, CD18 measurement entails its pitfalls. Here we present a cohort of ten LAD patients and a review of the relevant literature illustrating the difficulties in sole reliance on CD18 measurement for initial diagnosis. These include normal range expression in some mutations, great variability between patients with the same mutation and subjective interpretation of results. We think there is a need for additional markers as part of the initial LAD diagnostic algorithm. We suggest CD11a expression, which was near absent in all patients in our cohort. The dual use of CD18 and CD11a can increase testing sensitivity and prevent delayed diagnosis of LAD-1.
Similar content being viewed by others
References
Van de Vijver E, van den Berg TK, Kuijpers TW. Leukocyte adhesion deficiencies. Hematol Oncol Clin. 2013;27:101–16.
Etzioni A. Genetic etiologies of leukocyte adhesion defects. Curr Opin Immunol. 2009;21:481–6.
Movahedi M, Entezari N, Pourpak Z, Mamishi S, Chavoshzadeh Z, Gharagozlou M, et al. Clinical and laboratory findings in Iranian patients with leukocyte adhesion deficiency. J Clin Immunol. 2007;27:302–7.
Van de Vijver E, Maddalena A, Sanal Ö, Holland SM, Uzel G, Madkaikar M, et al. Hematologically important mutations: leukocyte adhesion deficiency (first update). Blood Cells Mol Dis. 2012;48:53–61.
Hibbs ML, Warldlaw AJ, Stacker SA, Anderson DC, Lee A, Roberts TM, et al. Transfection of cells from patients with leukocyte adhesion deficiency with an integrin β subunit (CD18) restores lymphocyte function-associated antigen-1 expression and function. J Clin Invest. 1990;85:674–81.
Desroches CV, Andréoni C, Rigal D. Differential expression of the LFA-1 molecule on the human peripheral blood mononuclear cell subpopulations. Immunol Lett. 1990;24:13–20.
Tan S-M. The leucocyte β2 (CD18) integrins: the structure, functional regulation and signalling properties. Biosci Rep. 2012;32:241–69.
Madkaikar MR, Gupta M, Rao M, Ghosh K. Prenatal diagnosis of LAD-I on cord blood by flowcytometry. Indian J Pediatr. 2012;79:1605–9.
Roos D, Meischl C, De Boer M. Genetic analysis of patients with leukocyte adhesion deficiency: genomic sequencing reveals otherwise undetectable mutations. Exp Hematol. 2002;30:252–61.
El-Sayed ZA, El-Ghoneimy DH, Abd-Allah H, Afifi HM. A rare association between leukocyte adhesion deficiency type I and psoriasis in humans. Allergy Asthma Immunol Res. 2011;3:138–40.
Hixson P, Smith CW, Shurin SB, Tosi MF. Unique CD18 mutations involving a deletion in the extracellular stalk region and a major truncation of the cytoplasmic domain in a patient with leukocyte adhesion deficiency type 1. Blood. 2004;103:1105–13.
Simon AJ, Lev A, Wolach B, Gavrieli R, Amariglio N, Rosenthal E, et al. The effect of gentamicin-induced readthrough on a novel premature termination codon of CD18 leukocyte adhesion deficiency patients. PLoS One. 2010;5:e13659.
Madkaikar M, Italia K, Gupta M, Chavan S, Mishra A, Rao M, et al. Molecular characterization of leukocyte adhesion deficiency-I in Indian patients: identification of 9 novel mutations. Blood Cells Mol Dis. 2015;54:217–23.
Parvaneh N, Mamishi S, Rezaei A, Rezaei N, Tamizifar B, Parvaneh L, et al. Characterization of 11 new cases of leukocyte adhesion deficiency type 1 with seven novel mutations in the ITGB2 gene. J Clin Immunol. 2010;30:756–60.
Harris E. Lessons from rare maladies: leukocyte adhesion deficiency syndromes. Curr Opin. 2013;20:16–25.
Tone Y, Wada T, Shibata F, Toma T, Hashida Y, Kasahara Y, et al. Somatic revertant mosaicism in a patient with leukocyte adhesion deficiency type 1. Blood. 2009;109:1182–4.
Vasconcelos Dde M, Beitler B, Martinez GA, Pereira J, Amigo Filho JU, Klautau GB, et al. CD18 deficiency evolving to megakaryocytic (M7) acute myeloid leukemia: case report. Blood cells Mol Dis. 2014;53:180–4.
Madkaikar M, Italia K, Gupta M, Desai M, Aggarwal A, Singh S, et al. Leukocyte adhesion deficiency-I with a novel intronic mutation presenting with pyoderma gangrenosum-like lesions. J Clin Immunol. 2015;35:431–4.
Dimanche MT, Le Deist F, Fischer A, Arnaout MA, Griscelli C, Lisowska-Grospierre B. LFA-1 β-chain synthesis and degradation in patients with leukocyte-adhesive proteins deficiency. Eur J Immunol. 1987;17:417–9.
Ding ZM, Babensee JE, Simon SI, Lu H, Perrard JL, Bullard DC, et al. Relative contribution of LFA-1 and Mac-1 to neutrophil adhesion and migration. J Immunol. 1999;163:5029–38.
Arnaout M. Structure and function of the leukocyte adhesion molecules CD11/CD18. Blood. 1990;75:1037–50.
Al-Dhekri H, Al-Mousa H, Ayas M, Al-Muhsen S, Al-Ghonaium A, Al-Ghanam G, et al. Allogeneic hematopoietic stem cell transplantation in leukocyte adhesion deficiency type 1: a single center experience. Biol Blood Marrow Transplant. 2011;17:1245–9.
Author information
Authors and Affiliations
Corresponding author
Additional information
Sarina Levy-Mendelovich and Erez Rechavi have contributed equally to this work.
Rights and permissions
About this article
Cite this article
Levy-Mendelovich, S., Rechavi, E., Abuzaitoun, O. et al. Highlighting the problematic reliance on CD18 for diagnosing leukocyte adhesion deficiency type 1. Immunol Res 64, 476–482 (2016). https://doi.org/10.1007/s12026-015-8706-5
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12026-015-8706-5